Diabetes mellitus is a generic term of metabolic disorders characterized by persistence of a hyperglycemic state due to the deficiency of insulin action. Diabetes mellitus is caused by combination in any degrees of reduced insulin sensitivity with reduced insulin secretion to cause characteristic abnormalities in carbohydrate, lipid and protein metabolisms. Recently, diabetes mellitus is said to be one of lifestyle-related diseases and is regarded as a disease expected to be ameliorated by appropriate therapy. However, when diabetes mellitus becomes severe, complications such as neuropathy, retinopathy, and nephropathy are generated, and movements in everyday life may be significantly reduced.
Diabetes mellitus is classified roughly into insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). IDDM is a type of diabetes mellitus in which pancreatic β-cells are necrotized, or arrested functions, by an autoimmune mechanism caused by a virus or the like, thereby failing to synthesize and secrete insulin. NIDDM is a type of diabetes mellitus in which hyperglycemia is manifested due to insufficient insulin secretion and insulin resistance caused by uncertain and diverse factors such as aging and stress. About 90% of patients with diabetes mellitus fall under NIDDM.
In therapy of patients with mild or moderate non-insulin-dependent diabetes mellitus, diet therapy and exercise therapy are mainly adopted. For example, the stabilization of blood glucose level is attempted by calorie restriction in meal and by improvement of carbohydrate metabolism with exercise. From the viewpoint of prevention of diabetes mellitus or prevention of ingravescence thereof, there has been demand for further development of diet therapy with a food capable of preventing diabetes mellitus or preventing ingravescence thereof.
If a rapid increase in blood glucose level after meal and its continuance (hyperglycemia after meal) continue for many years, abnormal glucose tolerance will sooner or later result to exacerbate diabetes mellitus. Exacerbation of diabetes mellitus is accompanied by promotion of angiopathy, which can lead to development of neurosis, nephropathy and retinopathy and to further complications of myocardial infarction and apoplexy. Suppression of hyperglycemia after meal is regarded as effective in treatment of NIDDM, and α-glucosidase inhibitors are used as carbohydrates absorption inhibitors, and medical pharmaceutical preparations such as sulfonylurea agents are used as insulin secretagogues. Under these circumstances, pharmaceutical preparations that prevent diabetes mellitus or prevent ingravescence thereof have also been desired in the field of pharmaceutical preparations.
There is insulin as a biological material that can suppress an elevation of blood glucose level. Insulin is a sole hormone in the living body, which decreases the level of blood glucose, for example by causing promotion of carbohydrate metabolism in the liver and enhancement of glucose uptake into muscle cells and fat cells. The glucose incorporated into muscle or fat cells is metabolized to glycogen to be stored in tissues. Translocation (recruitment), to a cell membrane, of glucose transporter-4 (GLUT-4) present in an intracellular pool can be mentioned as one mode of action of insulin in muscle or fat cells. The signal transduction mechanism involved in glucose uptake in muscle or fat cells by insulin is estimated at present as follows:
That is, insulin binds to an insulin receptor (IR) on a cell membrane and then activates a tyrosine kinase in an intracellular moiety of IR to tyrosine-phosphorylate a family of insulin receptor substrates (IRSs). The tyrosine-phosphorylated IRSs activate phosphatidylinositol 3-kinase (PI3K), followed by some signal transductions, to translocate intracellular latent GLUT-4 to a cell membrane (see, for example, N. Engl. J. Med., 341, 248-257, 1999). This insulin is also used as a pharmaceutical preparation to prevent diabetes mellitus or prevent ingravescence thereof.
As described above, abnormalities in carbohydrate metabolism are related to many lifestyle-related diseases, and thus there is necessity for foods and pharmaceutical preparations aimed at preventing lifestyle-related diseases or preventing ingravescence thereof.
Physical strength, particularly endurance, anti-fatigue strength and fatigue-relieving strength become important in the field of sports. The fatigue of muscles by exercise occurs when glycogen serving as a source of energy production in tissues is consumed to a certain limit. That is, when glycogen in tissues is exhausted, muscles become unable to move. A positive correlation between glycogen stores in tissues and endurance has been reported (see, for example, Acta Physiol. Scand., 71, 140-150, 1967). Accordingly, it is important to increase glycogen stores in tissues in order to enhance endurance, anti-fatigue strength, fatigue-relieving strength, etc.
Under these circumstances, it has been reported as a result of recent studies that for example, substances having an action of promoting glucose uptake into cells are discovered in microorganism-derived, low-molecular substances or in plant extracts (see, for example, Science, 284, 974-977, 1999). In addition, milk whey protein and its hydrolysates for example are reported to have an effect of storing glycogen (see, for example, Japanese Patent Application Laid-Open No. 2005-289861). Further, it has already been reported that milk protein hydrolysates have an action of reducing the level of blood glucose to exert a therapeutic effect on diabetes mellitus (see, for example, Japanese Patent Application Laid-Open z4-149139), and that milk whey protein hydrolysates have an action of regulating blood glucose (see, for example, Japanese Patent Application National Publication (Laid-Open) No. 2006-510367).